A negatively charged cluster in the disordered acidic domain of GPIHBP1 provides selectivity in the interaction with lipoprotein lipase.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
30
04
2024
accepted:
16
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
GPIHBP1 is a membrane protein of endothelial cells that transports lipoprotein lipase (LPL), the key enzyme in plasma triglyceride metabolism, from the interstitial space to its site of action on the capillary lumen. An intrinsically disordered highly negatively charged N-terminal domain of GPIHBP1 contributes to the interaction with LPL. In this work, we investigated whether the plethora of heparin-binding proteins with positively charged regions found in human plasma affect this interaction. We also wanted to know whether the role of the N-terminal domain is purely non-specific and supportive for the interaction between LPL and full-length GPIHBP1, or whether it participates in the specific recognition mechanism. Using surface plasmon resonance, affinity chromatography, and FRET, we were unable to identify any plasma component, besides LPL, that bound the N-terminus with detectable affinity or affected its interaction with LPL. By examining different synthetic peptides, we show that the high affinity of the LPL/N-terminal domain interaction is ensured by at least ten negatively charged residues, among which at least six must sequentially arranged. We conclude that the association of LPL with the N-terminal domain of GPIHBP1 is highly specific and human plasma does not contain components that significantly affect this complex.
Identifiants
pubmed: 39179764
doi: 10.1038/s41598-024-70468-6
pii: 10.1038/s41598-024-70468-6
doi:
Substances chimiques
Lipoprotein Lipase
EC 3.1.1.34
GPIHBP1 protein, human
0
Receptors, Lipoprotein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19639Subventions
Organisme : Tallinna Tehnikaülikool
ID : SS22005
Organisme : Tallinna Tehnikaülikool
ID : SS22005
Organisme : Tallinna Tehnikaülikool
ID : SS22005
Organisme : Tallinna Tehnikaülikool
ID : SS22005
Informations de copyright
© 2024. The Author(s).
Références
Davies, B. S. et al. GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries. Cell Metab. https://doi.org/10.1016/j.cmet.2010.04.016 (2010).
doi: 10.1016/j.cmet.2010.04.016
pubmed: 20620994
pmcid: 2913606
Song, W. et al. The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing. Proc. Natl. Acad. Sci. https://doi.org/10.1073/pnas.2313825120 (2023).
doi: 10.1073/pnas.2313825120
pubmed: 38150477
pmcid: 10786293
Song, W. et al. Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells. J. Clin. Investig. https://doi.org/10.1172/jci157500 (2022).
doi: 10.1172/jci157500
pubmed: 36519543
pmcid: 9754003
Reimund, M. et al. Evidence for two distinct binding sites for lipoprotein lipase on glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1). J. Biol. Chem. 290(22), 13919–13934. https://doi.org/10.1074/jbc.m114.634626 (2015).
doi: 10.1074/jbc.m114.634626
pubmed: 25873395
pmcid: 4447966
Mysling, S. et al. The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain. eLife. https://doi.org/10.7554/eLife.12095 (2016).
doi: 10.7554/eLife.12095
pubmed: 27929370
pmcid: 5148603
Kristensen, K. et al. A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase. Proc. Natl. Acad. Sci. U.S.A. https://doi.org/10.1073/pnas.1806774115 (2018).
doi: 10.1073/pnas.1806774115
pubmed: 30559189
pmcid: 6358717
Holmes, R. & Cox, L. Comparative studies of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1: evidence for a eutherian mammalian origin for the GPIHBP1 gene from an LY6-like gene. 3 Biotech. https://doi.org/10.1007/s13205-011-0026-4 (2012).
doi: 10.1007/s13205-011-0026-4
pubmed: 22582156
pmcid: 3482443
Birrane, G. et al. Structure of the lipoprotein lipase–GPIHBP1 complex that mediates plasma triglyceride hydrolysis. Proc. Natl. Acad. Sci. U.S.A. https://doi.org/10.1073/pnas.1817984116 (2019).
doi: 10.1073/pnas.1817984116
pubmed: 30850549
pmcid: 6442593
Arora, R. et al. Structure of lipoprotein lipase in complex with GPIHBP1. Proc. Natl. Acad. Sci. U.S.A. https://doi.org/10.1073/pnas.1820171116 (2019).
doi: 10.1073/pnas.1820171116
pubmed: 31871169
pmcid: 6955382
van Tilbeurgh, H., Roussel, A., Lalouel, J. & Cambillau, C. Lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray structure: consequences for heparin binding and catalysis. J. Biol. Chem. https://doi.org/10.1016/S0021-9258(17)41822-9 (1994).
doi: 10.1016/S0021-9258(17)41822-9
pubmed: 8308035
Lookene, A., Chevreuil, O., Østergaard, P. & Olivecrona, G. Interaction of lipoprotein lipase with heparin fragments and with heparan sulfate: Stoichiometry, stabilization, and kinetics. Biochemistry. https://doi.org/10.1021/bi960008e (1996).
doi: 10.1021/bi960008e
pubmed: 8810923
Larnkjaer, A., Nykjaer, A., Olivecrona, G., Thøgersen, H. & Ostergaard, P. B. Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to alpha 2-macroglobulin-receptor/low-density-lipoprotein-receptor-related protein by heparin fragments. Biochem. J. https://doi.org/10.1042/bj3070205 (1995).
doi: 10.1042/bj3070205
pubmed: 7717977
pmcid: 1136764
Spillmann, D., Lookene, A. & Olivecrona, G. Isolation and characterization of low sulfated heparan sulfate sequences with affinity for lipoprotein lipase. J. Biol. Chem. https://doi.org/10.1074/jbc.M604702200 (2006).
doi: 10.1074/jbc.M604702200
pubmed: 16807244
Young, E., Cosmi, B., Weitz, J. & Hirsh, J. Comparison of the non-specific binding of unfractionated heparin and low molecular weight heparin (Enoxaparin) to plasma proteins. Thromb Haemost. 70(4), 625–630 (1993) (PubMed PMID: 8115988).
doi: 10.1055/s-0038-1649639
pubmed: 8115988
Killeen, R., Wait, R., Begum, S., Gray, E. & Mulloy, B. Identification of major heparin-binding proteins in plasma using electrophoresis and mass spectrometry. Int. J. Exp. Pathol. https://doi.org/10.1111/j.0959-9673.2004.390af.x (2004).
doi: 10.1111/j.0959-9673.2004.390af.x
pmcid: 2517482
Zammit, A., Pepper, D. S. & Dawes, J. Interaction of immobilised unfractionated and LMW heparins with proteins in whole human plasma. Thromb Haemost. 70(6), 951–958 (1993) (PubMed PMID: 8165617).
doi: 10.1055/s-0038-1649706
pubmed: 8165617
Xu, D. & Esko, J. D. Demystifying heparan sulfate-protein interactions. Annu. Rev. Biochem. https://doi.org/10.1146/annurev-biochem-060713-035314 (2014).
doi: 10.1146/annurev-biochem-060713-035314
pubmed: 24606135
pmcid: 7851832
Bengtsson-Olivecrona, G. & Olivecrona, T. Phospholipase activity of milk lipoprotein lipase. Method. Enzymol. 197, 345–356 (1991).
doi: 10.1016/0076-6879(91)97160-Z
Gill, S. & von Hippel, P. Calculation of protein extinction coefficients from amino acid sequence data. Anal. Biochem. https://doi.org/10.1016/0003-2697(89)90602-7 (1989).
doi: 10.1016/0003-2697(89)90602-7
pubmed: 2610349
Damen, J., Dijkstra, J., Regts, J. & Scherphof, G. Effect of lipoprotein-free plasma on the interaction of human plasma high density lipoprotein with egg yolk phosphatidylcholine liposomes. Biochimica et Biophysica Acta (BBa) - Lipids and Lipid Metabolism. https://doi.org/10.1016/0005-2760(80)90188-5 (1980).
doi: 10.1016/0005-2760(80)90188-5
pubmed: 7191326
Gunn, K. H., Neher, S. B., Gunn, K. H. & Neher, S. B. Structure of dimeric lipoprotein lipase reveals a pore adjacent to the active site. Nat. Commun. https://doi.org/10.1038/s41467-023-38243-9 (2023).
doi: 10.1038/s41467-023-38243-9
pubmed: 37142573
pmcid: 9968307
Mirdita, M. et al. ColabFold: making protein folding accessible to all. Nat. Methods. https://doi.org/10.1038/s41592-022-01488-1 (2022).
doi: 10.1038/s41592-022-01488-1
pubmed: 35637307
pmcid: 9184281
Evans, R. et al. Protein complex prediction with AlphaFold-Multimer. bioRxiv. https://doi.org/10.1101/2021.10.04.463034 (2022).
doi: 10.1101/2021.10.04.463034
pubmed: 36299433
pmcid: 9603827
Consortium TU et al. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res. https://doi.org/10.1093/nar/gkac1052 (2023).
doi: 10.1093/nar/gkac1052
Meng, E. C. et al. UCSF ChimeraX: Tools for structure building and analysis. Protein Sci. https://doi.org/10.1002/pro.4792 (2023).
doi: 10.1002/pro.4792
pubmed: 37774136
pmcid: 10588335
Risti, R. et al. Combined action of albumin and heparin regulates lipoprotein lipase oligomerization, stability, and ligand interactions. PLOS ONE. https://doi.org/10.1371/journal.pone.0283358 (2023).
doi: 10.1371/journal.pone.0283358
pubmed: 37043509
pmcid: 10096250
Leth-Espensen, K. Z. et al. The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding. Proc. Natl. Acad. Sci. https://doi.org/10.1073/pnas.2026650118 (2021).
doi: 10.1073/pnas.2026650118
pubmed: 33723082
pmcid: 8000434
Necci, M., Piovesan, D., Predictors, C., Curators, D. & Tosatto, S. C. E. AlphaFold and implications for intrinsically disordered proteins. J. Mol. Biol. https://doi.org/10.1016/j.jmb.2021.167208 (2021).
doi: 10.1016/j.jmb.2021.167208
pubmed: 33647288
Doolittle, R. F. Biosynthesis Metabolism, Alterations in Disease. In The Plasma Proteins 2nd edn, Vol. II (ed. Putnam, F. W.) 148–9 (Academic Press, New York, 1975).
Olson, S. T., Halvorson, H. R. & Björk, I. Quantitative characterization of the thrombin-heparin interaction. Discrimination between specific and nonspecific binding models. J. Biol. Chem. https://doi.org/10.1016/S0021-9258(18)38124-9 (1991).
doi: 10.1016/S0021-9258(18)38124-9
pubmed: 1939192
Du, X. et al. Insights into protein-ligand interactions: Mechanisms, models, and methods. Int. J. Mol. Sci. https://doi.org/10.3390/ijms17020144 (2016).
doi: 10.3390/ijms17020144
pubmed: 28042825
pmcid: 5297639
Wallerstein, J. et al. Entropy-entropy compensation between the protein, ligand, and solvent degrees of freedom fine-tunes affinity in ligand binding to galectin-3C. JACS Au. https://doi.org/10.1021/jacsau.0c00094 (2021).
doi: 10.1021/jacsau.0c00094
pubmed: 34467311
pmcid: 8395690